PPARα/γ signaling pathways are involved in Chlamydia pneumoniae-induced foam cell formation via upregulation of SR-A1 and ACAT1 and downregulation of ABCA1/G1

Chlamydia pneumoniae (Cpn) has been reported to be involved in the pathogenesis of early atherosclerosis by inducing macrophage-derived foam cell formation in the presence of low-density lipoprotein (LDL). However, the biochemical mechanisms underlying Cpn-induced foam cell formation are still not fully elucidated. The present study showed that in LDL-treated THP-1-derived macrophages, Cpn not only upregulated the expression of scavenger receptor A1 (SR-A1) and acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1), but it also downregulated the expression of ATP binding cassette transporters (ABCA1 and ABCG1) at both the mRNA and protein levels. These processes facilitated cholesterol accumulation and promoted macrophage-derived foam cell formation. Treatment with the peroxisome proliferator-activated receptor (PPAR)-gamma agonist rosiglitazone or the PPAR alpha agonist fenofibrate decreased the number of foam cells induced by Cpn, while the PPAR gamma antagonist GW9662, the PPAR alpha antagonist MK886, or PPAR alpha/gamma siRNAs enhanced the effect of Cpn on foam cell formation and gene expression of SR-A1, ACAT1, and ABCA1/G1. Moreover, the PPAR gamma agonist rosiglitazone reversed the downregulation of CD36 by Cpn, while PPAR gamma siRNA and the PPAR gamma inhibitor GW9662 further suppressed CD36 expression. However, the PPAR alpha agonist, inhibitor, and siRNA all showed no effect on CD36 expression. In conclusion, the PPAR alpha and PPAR gamma pathways are both involved in Cpn-induced macrophage-derived foam cell formation by upregulating SR-A1 and ACAT1 and downregulating ABCA1/G1 expression.

Automated summary

The biochemical mechanisms of Chlamydia pneumoniae (Cpn)-induced foam cell formation in early atherosclerosis involve upregulation of SR-A1 and ACAT1, as well as downregulation of ABCA1/G1 expression by both PPAR alpha and PPAR gamma pathways.